Journal article
Accelerated Blood Clearance Phenomenon Reduces the Passive Targeting of PEGylated Nanoparticles in Peripheral Arterial Disease
ACS applied materials & interfaces, Vol.8(28), pp.17955-17963
07/20/2016
DOI: 10.1021/acsami.6b05840
PMCID: PMC4959540
PMID: 27340833
Abstract
Peripheral arterial disease (PAD) is a leading global health concern. Due to limited imaging and therapeutic options, PAD and other ischemia-related diseases may benefit from the use of long circulating nanoparticles as imaging probes and/or drug delivery vehicles. Polyethylene glycol (PEG)-conjugated nanoparticles have shown shortened circulation half-lives in vivo when injected multiple times into a single subject. This phenomenon has become known as the accelerated blood clearance (ABC) effect. The phenomenon is of concern for clinical translation of nanomaterials as it limits the passive accumulation of nanoparticles in many diseases, yet it has not been evaluated using inorganic or organic-inorganic hybrid nanoparticles. Herein, we found that the ABC phenomenon was induced by reinjection of PEGylated long circulating organic-inorganic hybrid nanoparticles, which significantly reduced the passive targeting of (64)Cu-labeled PEGylated reduced graphene oxide-iron oxide nanoparticles ((64)Cu-RGO-IONP-PEG) in a murine model of PAD. Positron emission tomography (PET) imaging was performed at 3, 10, and 17 days postsurgical induction of hindlimb ischemia. At day 3 postsurgery, the nanoparticles displayed a long circulation half-life with enhanced accumulation in the ischemic hindlimb. At days 10 and 17 postsurgery, reinjected mice displayed a short circulation half-life and lower accumulation of the nanoparticles in the ischemic hindlimb, in comparison to the naïve group. Also, reinjected mice showed significantly higher liver uptake than the naïve group, indicating that the nanoparticles experienced higher sequestration by the liver in the reinjected group. Furthermore, photoacoustic (PA) imaging and Prussian blue staining confirmed the enhanced accumulation of the nanoparticles in the liver tissue of reinjected mice. These findings validate the ABC phenomenon using long circulating organic-inorganic hybrid nanoparticles upon multiple administrations to the same animal, which may provide valuable insight into the future clinical applications of nanoparticles for imaging and treatment of PAD.
Details
- Title: Subtitle
- Accelerated Blood Clearance Phenomenon Reduces the Passive Targeting of PEGylated Nanoparticles in Peripheral Arterial Disease
- Creators
- Hyung-Jun Im - University of Wisconsin–MadisonChristopher G England - University of Wisconsin–MadisonLiangzhu Feng - Soochow UniversityStephen A Graves - University of Wisconsin–MadisonReinier Hernandez - University of Wisconsin–MadisonRobert J Nickles - University of Wisconsin–MadisonZhuang Liu - Soochow UniversityDong Soo Lee - Seoul National UniversitySteve Y Cho - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- ACS applied materials & interfaces, Vol.8(28), pp.17955-17963
- DOI
- 10.1021/acsami.6b05840
- PMID
- 27340833
- PMCID
- PMC4959540
- NLM abbreviation
- ACS Appl Mater Interfaces
- ISSN
- 1944-8244
- eISSN
- 1944-8252
- Grant note
- T32 GM008349 / NIGMS NIH HHS R01 EB021336 / NIBIB NIH HHS T32 CA009206 / NCI NIH HHS R01 CA169365 / NCI NIH HHS S10 OD018505 / NIH HHS P30 CA014520 / NCI NIH HHS
- Language
- English
- Date published
- 07/20/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383914302771
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